gpc2 car t cells for relapsed or refractory neuroblastoma

Conditions: Refractory Neuroblastoma; Relapsed Neuroblastoma; High-risk Neuroblastoma

Summary: this is a first in human dose escalation trial to determine the safety of administering gpc2 car t cells in patients with advanced neuroblastoma.

despite the use of intensive multimodal chemoradiotherapy, surgery, autologous stem cell transplant and disialoganglioside antigen (gd2)-targeted immunotherapy for the treatment of patients with high-risk neuroblastoma, approximately 60% of children still die from this disease and survivors suffer lifelong treatment related comorbidities. for patients who suffer a relapse after receiving therapy with standard of care multimodality treatment, there are no known curative options. glypican 2 (gpc2) is highly expressed on the plasma membrane of most high-risk neuroblastomas, is further enriched in the tumor stem cell compartment, but is not expressed at significant levels on normal tissues, making it an ideal target for immune directed therapies. to therapeutically leverage gpc2's differential expression, a gpc2-directed car t cell therapy that potently inhibits the growth of neuroblastoma patient-derived xenografts has been developed. this investigation will be a single institution, open-label first in human, dose escalation and expansion study designed to assess the safety, tolerability, and manufacturing feasibility of gpc2 car t cells.

Eligibility criteria:
inclusion criteria: 1. signed informed consent form 2. ≥ 1 year of age 3. disease status 1. patients must have high-risk neuroblastoma according to children's oncology group risk classification at the time of study enrollment. 2. histologically confirmed diagnosis of neuroblastoma that is recurrent/relapsed/persistent according to international neuroblastoma response criteria 3. patients must have evaluable or measurable disease at enrollment 4. adequate organ function 5. adequate performance status defined as lanksy or karnofsky performance score ≥60. 6. subjects of reproductive potential must agree to use acceptable birth control methods. exclusion criteria: 1. patients with active hepatitis b or active hepatitis c. 2. patients with hiv infection. 3. patients with uncontrolled active infection 4. patients with primary or acquired immunodeficiency disorder. 5. concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well. 6. patients with actively progressing central nervous system metastases, including parenchymal or leptomeningeal involvement. 7. active medical disorder that, in the opinion of the investigator, would substantially increase. the risk of uncontrollable cytokine release syndrome and/or neurotoxicity. 8. patients with congestive heart failure (as defined by new york heart association functional classification iii or iv), unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to study entry or a history of myocarditis. 9. patients who have received any live vaccines within 30 days prior to enrollment. 10. pregnant or nursing (lactating) women.